Psychotherapy of the lived space: a phenomenological and ecological concept.
Using phenomenological and ecological psychology as a base, the author develops the concept of lived space as the totality of an individual's spatial and social relationships, including his "horizon of possibilities". The lived space may also be regarded as the individual's ecological niche, which is continuously shaped by his exchange with the environment. Mental illness may then be conceived as a limitation or deformation of the patient's lived space, inhibiting his responsivity and exchange with the environment. Unconscious dysfunctional patterns of feeling and behaving act as "blind spots" or "curvatures" in lived space and lead to typical distortions, thereby further restricting the patient's potentialities and development. Accordingly, the task of psychotherapy is to explore and understand the patient's lived space in order to reopen his horizon of possibilities. The main agent for this purpose is the interactive field of psychotherapy, which may be regarded as a "fusion of horizons" of the patient's and the therapist's worlds.


Nutritional evaluation of different varieties of sorghum and the effects on nursery pig growth performance.
Five experiments were conducted to determine the standardized total tract digestibility (STTD) of P, digestible energy (DE), metabolizable energy (ME), and standardized ileal digestibility (SID) of amino acids (AA) in three sorghum varieties compared with corn and to determine the effects of sorghum varieties on nursery pig growth. In exp. 1, 48 barrows (initially 18.6 kg) were housed individually in metabolism crates. Treatments were arranged in a 2 × 4 factorial evaluating two levels of microbial phytase (0 or 500 units/kg) and four grain sources (corn, high-lysine, red, or white sorghum). Added phytase improved (P < 0.05) STTD of P in all ingredients, but was not different among the grains. In exp. 2, the DE and ME in the three sorghum varieties were not different from corn. In exp. 3, 10 growing barrows (initially 25.9 kg) with a T-cannula in the terminal ileum were used. Standardized ileal digestible Lys, Met, Thr, and Val were greater (P < 0.05) in corn than in the sorghum-based diets with no differences among the sorghum varieties. In exp. 4, 160 pigs (initially 6.3 kg) were randomly allotted to one of four dietary treatments with five pigs per pen and eight replicate pens per treatment in a 20-d experiment. Dietary treatments included corn or the three sorghum varieties, where the varieties of sorghum replaced corn on an SID Lys basis. No differences among treatments were observed in any growth performance parameters. In exp. 5, treatments consisted of a corn-based diet, a diet based on conventional sorghum (a mixture of red and white sorghum), and four diets with high-lysine sorghum containing increasing amounts of feed-grade AA, replacing soybean meal. Overall, pigs fed the high-lysine sorghum diet with the greatest amount of added feed-grade AA had the poorest gain:feed ratio (G:F; P < 0.05) compared with pigs fed all the other experimental diets. Within those fed the high-lysine sorghum and feed-grade AA, average daily gain, final body weight (linear, P < 0.10), and G:F (linear, P < 0.01) decreased as feed-grade AA increased. In summary, no differences in STTD of P or in DE and ME were observed among the grain sources. The SID AA values for the three sorghum varieties were not different; however, they were all lower than for corn. These results indicate that these varieties of sorghum can successfully replace corn in nursery pig diets if diets are formulated to account for differences in AA digestibility.


The inhibitory effect of Acyclovir loaded nano-niosomes against herpes simplex virus type-1 in cell culture.
Wide distribution and low half-life of acyclovir has led to a high dose consumption of the drug. Recent studies have shown that encapsulation of acyclovir in nano-carriers can increase effectiveness and decrease its side effects. We investigated the inhibitory effect of acyclovir loaded nano-niosomes against herpes simplex virus type-1 (HSV-1) in cell culture. In-vitro cytotoxicity study of empty niosomes (E-N), acyclovir loaded niosomes (ACV-N) and ACV as a free drug against HeLa cell line was performed by MTT assay and the viral titers was tested by TCID50 assay. The results indicated that a significant higher antiviral activity for acyclovir loaded nano-niosomes of about 3 times in comparison with free drug. The results of this study revealed ACV-N have a higher antiviral activity compared with free drug; it could be a suitable carrier for delivery of acyclovir in the treatment of HSV-1 infections.


Isocaloric carbohydrate versus carbohydrate-protein ingestion and cycling time-trial performance.
This study was designed to compare the effects of energy-matched carbohydrate (CHO) and carbohydrate-protein (CHO-PRO) supplements on cycling time-trial performance. Twelve competitive male cyclists and triathletes each completed 2 trials in a randomized and counterbalanced order that were separated by 5-10 d and applied in a double-blind manner. Participants performed a 45-min variable-intensity exercise protocol on a cycle ergometer while ingesting either a 9% CHO solution or a mixture of 6.8% CHO plus 2.2% protein in volumes providing 22 kJ/kg body mass. Participants were then asked to cycle 6 km in the shortest time possible. Blood glucose and lactate concentrations were measured every 15 min during exercise, along with measures of substrate oxidation via indirect calorimetry, heart rate, and ratings of perceived exertion. Mean time to complete the 6-km time trial was 433 + or - 21 s in CHO trials and 438 + or - 22 s in CHO-PRO trials, which represents a 0.94% (CI: 0.01, 1.86) decrement in performance with the inclusion of protein (p = .048). However, no other variable measured in this study was significantly different between trials. Reducing the quantity of CHO included in a supplement and replacing it with protein may not represent an effective nutritional strategy when the supplement is ingested during exercise. This may reflect the central ergogenic influence of exogenous CHO during such activity.


State of Tyr49 in a mutant tryptophan synthase alpha-subunit substituted at position 49.
The states of tyrosine residues in an alpha-subunit of wild-type tryptophan synthase from Escherichia coli and a mutant protein which has tyrosine in place of glutamic acid at position 49, were examined by absorption spectrum, spectrophotometric titration of phenolic hydroxyl ionization, and deuteration kinetics of phenolic hydrogen monitored by fluorescence measurement. The difference absorption spectrum of the mutant protein against the wild-type protein at pH 7.0 and 25 degrees C had peaks at 289, 282, and 276.5 nm. These positions corresponded to those in the absorption spectrum of L-tyrosine derivatives in a non-aqueous solvent at 77 K and these bands were well-resolved even at 25 degrees C as if the tyrosine residue were fixed at lower temperature. The titration curve of the mutant protein at 3 degrees C differed from that of the wild-type protein only above pH 12.7, where the difference molar extinction coefficient at 295 nm reached a plateau, indicating that ionization of Tyr49 took place at an abnormally high pH. These results suggest that Tyr49 is buried in the hydrophobic interior and fixed in a certain orientation. The deuterium exchanges of phenolic hydrogen at pH 7.0 and 13 degrees C in the wild-type and mutant proteins consisted of a single and two first order processes, respectively, all three having smaller rate constants than that of free tyrosine, indicating that these tyrosine residues are buried. It is concluded that Tyr49 in the mutant protein is not on the surface of the molecule.


Mortality in Barrett's oesophagus: results from a population based study.
Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231)) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.


The Functional Foundations of Episodic Memory Remain Stable Throughout the Lifespan.
It has been suggested that specific forms of cognition in older age rely largely on late-life specific mechanisms. Here instead, we tested using task-fMRI (n = 540, age 6-82 years) whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural, and evolutionary influences. We clustered regions of the cerebral cortex according to the shape of the lifespan trajectory of memory activity in each region so that regions showing the same pattern were clustered together. The results revealed that lifespan trajectories of memory encoding function showed a continuity through life but no evidence of age-specific mechanisms such as compensatory patterns. Encoding activity was related to general cognitive abilities and variations of grey matter as captured by a multi-modal independent component analysis, variables reflecting core aspects of cognitive and structural change throughout the lifespan. Furthermore, memory encoding activity aligned to fundamental aspects of brain organization, such as large-scale connectivity and evolutionary cortical expansion gradients. Altogether, we provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only.


Limits on Supernova-Associated ^{60}Fe/^{26}Al Nucleosynthesis Ratios from Accelerator Mass Spectrometry Measurements of Deep-Sea Sediments.
We searched for the presence of ^{26}Al in deep-sea sediments as a signature of supernova influx. Our data show an exponential dependence of ^{26}Al with the sample age that is fully compatible with radioactive decay of terrigenic ^{26}Al. The same set of samples demonstrated a clear supernova ^{60}Fe signal between 1.7 and 3.2 Myr ago. Combining our ^{26}Al data with the recently reported ^{60}Fe data results in a lower limit of 0.18_{-0.08}^{+0.15} for the local interstellar ^{60}Fe/^{26}Al isotope ratio. It compares to most of the ratios deduced from nucleosynthesis models and is within the range of the observed average galactic ^{60}Fe/^{26}Al flux ratio of (0.15±0.05).


Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis.
Brain arteries are wrapped by vascular smooth muscle cells (VSMCs). Fully differentiated VSMCs are important for brain artery homeostasis, and they are lost in several cerebrovascular diseases. How healthy VSMCs differentiate on different brain arteries during development is unclear. Such knowledge will help regenerate lost VSMCs in brain arteriopathy. To answer this question, we studied the developmental muscularization of the zebrafish circle of Willis (CW) arteries, the major arterial loop that supplies blood to the brain in all vertebrates. We found that artery specification of CW endothelial cells (ECs) happens after they migrate from primitive veins to form CW arteries. VSMCs differentiate from pdgfrb+ common vascular mural cell progenitors at the time when embryo circulation starts and progress temporally and spatially from anterior to posterior CW arteries. Computational fluid dynamic simulation confirms that earlier VSMC differentiation coincide with higher pulsatile flow hemodynamics in anterior CW arteries. Pulsatile blood flow induces the differentiation of human brain pdgfrb+ progenitors into VSMCs and reducing pulsatile blood flow by blocking the zebrafish embryo heartbeat after pdgfrb+ recruitment but before VSMC differentiation limits the number of mature VSMCs. Congruently, the flow responsive transcription factor klf2a is activated in ECs before VSMC differentiation and knockdown delays VSMC differentiation on CW arteries. Overall, our data place hemodynamic activation of endothelial klf2a signaling as key determinant of spatiotemporal VSMC differentiation on CW arteries.


Interobserver variability of vertebral heart size measurements in dogs with normal and enlarged hearts.
The vertebral heart size (VHS) method by Buchanan is based on anatomic landmarks. A potential source of variation among observers is differences in the selection of measurement points. The objective was to test variability between observers with different levels of training in thoracic radiology and small animal clinical practice. Fifty sets of thoracic radiographs of cavalier King Charles spaniels, were divided into five groups; (Normal) normal cardiopulmonary structures, (I) slight cardiomegaly, (II) moderate cardiomegaly, (II +) moderate cardiomegaly with congestive heart failure, and (III +) severe cardiomegaly with congestive heart failure. Cardiomegaly was confirmed by echocardiography to be caused by mitral regurgitation because of myxomatous mitral valve disease. Sixteen observers representing four levels of experience (four observers/level) evaluated the radiographs; (1) European Diplomates in Veterinary Diagnostic Imaging, (2) Experienced small animal clinicians, (3) Trainees in small animal clinical practice (4) Veterinary students. Almost identical mean VHS values were found among the four experience levels for each of the five groups of radiographs with a low coefficient of variation, range 1.5-3.2%. Mean difference among the 16 observers was 1.05 +/- 0.32 vertebrae (v). Mean difference among individuals in each observer group was approximately 0.5 v for all but the groups of trainees were the difference was 0.6-0.9 v. The conclusion is that VHS method for heart size is independent of observer experience but dependent of individual observers selection of reference points and transformation of long and short axis dimensions into VHS units.


Influence of PCR reagents on DNA polymerase extension rates measured on real-time PCR instruments.
Radioactive DNA polymerase activity methods are cumbersome and do not provide initial extension rates. A simple extension rate assay would enable study of basic assumptions about PCR and define the limits of rapid PCR. A continuous assay that monitors DNA polymerase extension using noncovalent DNA dyes on common real-time PCR instruments was developed. Extension rates were measured in nucleotides per second per molecule of polymerase. To initiate the reaction, a nucleotide analog was heat activated at 95 °C for 5 min, the temperature decreased to 75 °C, and fluorescence monitored until substrate exhaustion in 30-90 min. The assay was linear with time for over 40% of the reaction and for polymerase concentrations over a 100-fold range (1-100 pmol/L). Extension rates decreased continuously with increasing monovalent cation concentrations (lithium, sodium, potassium, cesium, and ammonium). Melting-temperature depressors had variable effects. DMSO increased rates up to 33%, whereas glycerol had little effect. Betaine, formamide, and 1,2-propanediol decreased rates with increasing concentrations. Four common noncovalent DNA dyes inhibited polymerase extension. Heat-activated nucleotide analogs were 92% activated after 5 min, and hot start DNA polymerases were 73%-90% activated after 20 min. Simple DNA extension rate assays can be performed on real-time PCR instruments. Activity is decreased by monovalent cations, DNA dyes, and most melting temperature depressors. Rational inclusion of PCR components on the basis of their effects on polymerase extension is likely to be useful in PCR, particularly rapid-cycle or fast PCR.


Integrative Approaches to Sleep Management in Skin Disease: Systematic Review.
Dermatological conditions, especially when severe, can lead to sleep disturbances that affect a patient's quality of life. However, limited research exists on the efficacy of treatments for improving sleep parameters in skin conditions. The objective was to perform a systematic review of the literature on dermatological conditions and the treatments available for improving sleep parameters. A literature review was performed using the PubMed, Ovid MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases from 1945 to 2021. After filtering based on our exclusion criteria, studies were graded using the SORT (Strength of Recommendation Taxonomy) algorithm, and only those receiving a grade of "2" or better were included. In total, 25 treatment studies (n=11,025) assessing sleep parameters related to dermatological conditions were found. Dupilumab appeared to be the best-supported and most effective treatment for improving sleep in atopic dermatitis (AD) but had frequent adverse effects. Topical treatments for AD were mostly ineffective, but procedural treatments showed some promise. Treatments for other conditions appeared efficacious. The evaluation of sleep parameter changes in dermatological treatments is predominantly restricted to AD. Systemic interventions such as dupilumab and procedural interventions were the most efficacious. Sleep changes in other dermatoses were limited by a paucity of available studies. The inclusion of a sleep assessment component to a broader range of dermatological treatment studies is warranted.


Three-dimensional accuracy of endodontic access preparations using novel nonrestrictive static guides: A laboratory study.
This study compared the accuracy of traditional endodontic access to conservative access cavities prepared with or without novel nonrestrictive endodontic access guides by operators with different levels of clinical experience without visual aids, using a three-dimensional volumetric accuracy analysis method. The accuracy of the preparations was analysed using a novel 3D volumetric analysis by calculating the intersection and volume of the actual cavities to the planned model cavities. The experienced operator significantly outperformed the inexperienced operator in the free hand groups, while accuracy of conservative access cavities prepared using the novel guides were comparable and significantly higher than the other groups (p < 0.05). The results demonstrated clinical experience enhanced endodontic preparations accuracy and that nonrestrictive guides achieve accurate conservative access cavities which are independent of the operator skill level. Additionally, the three-dimensional volumetric analysis is a consistent and objective method to judge the accuracy of guided endodontic techniques.


Posttranscriptional regulation of surfactant protein-A messenger RNA in human fetal lung in vitro by glucocorticoids.
Surfactant protein-A (SP-A), the major pulmonary surfactant-associated protein, is a developmentally and hormonally regulated sialoglycoprotein of about 35,000 mol wt. In previous studies we observed that dexamethasone has dose-dependent biphasic effects on the levels of SP-A and its mRNA in human fetal lung in vitro. At concentrations of 10(-10)-10(-9) M, dexamethasone increased the levels of SP-A and its mRNA over those of control tissues, whereas at concentrations greater than or equal to 10(-8) M, the steroid was markedly inhibitory. Our findings suggest that the inhibitory action of dexamethasone (greater than 10(-8) M) on SP-A mRNA levels was mediated by an effect to reduce SP-A mRNA stability, since the steroid caused a dose-dependent increase in the rate of transcription; however, an effect to increase transcription with premature termination leading to instability of mRNA transcripts could not be ruled out. In the present investigation we have studied in detail the mechanisms underlying the biphasic effects of glucocorticoids on SP-A mRNA levels in human fetal lung tissues in vitro. Our findings indicate that dexamethasone (10(-7) M) has no adverse effect on the elongation of nascent mRNA transcripts throughout the SP-A gene; elongation of SP-A mRNA transcripts in dexamethasone-treated tissue explants was similar to that observed in tissues incubated in control medium or medium containing (Bu)2cAMP. Therefore, premature termination of SP-A mRNA transcription leading to the instability of SP-A mRNA can be ruled out. On the other hand, we found that dexamethasone (10(-7) M) had a pronounced effect to reduce the apparent half-life of SP-A mRNA; in control explants maintained in the presence of actinomycin-D to block gene transcription, the SP-A mRNA half-life was estimated to be 11.4 h, whereas in tissues also treated with dexamethasone, the SP-A mRNA half-life was reduced by more than 60% to 5.0 h. Dexamethasone also was found to have dose-dependent effects on the degradation of SP-A mRNA. After 12 h of incubation in the presence of actinomycin-D and dexamethasone at 10(-9) and 10(-7) M, the levels of SP-A mRNA were reduced by 50% and 80%, respectively, compared to those in tissue incubated with actinomycin-D alone. The inhibitory effects of glucocorticoids on SP-A mRNA levels were completely reversible and were blocked by the glucocorticoid antagonist RU486.(ABSTRACT TRUNCATED AT 400 WORDS)


[Consensus on the detection and management of prediabetes. Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society].
In Spain, according to the email@example.com study, 13.8% of the adult population suffers from diabetes and 14.8% from some form of prediabetes (impaired glucose tolerance, impaired fasting glucose or both). Since early detection of prediabetes can facilitate the implementation of therapeutic measures to prevent its progression to diabetes, we believe that preventive strategies in primary care and specialized clinical settings should be agreed. Screening for diabetes and prediabetes using a specific questionnaire (FINDRISC) and/or the measurement of fasting plasma glucose in high risk patients leads to detecting patients at risk of developing diabetes and it is necessary to consider how they should be managed. The intervention in lifestyle can reduce the progression to diabetes and reverse a prediabetic state to normal and is a cost-effective intervention. Some drugs, such as metformin, have also been shown effective in reducing the progression to diabetes but are not superior to non-pharmacological interventions. Finally, an improvement in some cardiovascular risk factors has been observed although there is no strong evidence supporting the effectiveness of screening in terms of morbility and mortality. The Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society has issued some recommendations that have been agreed by the Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Endocrinología Pediátrica, Sociedad Española de Farmacia Comunitaria, Sociedad Española de Medicina Familiar y Comunitaria, Sociedad Española de Médicos Generales, Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina Interna, Asociación de Enfermería Comunitaria and Red de Grupos de Estudio de la Diabetes en Atención Primaria.


Driving behavior of alcohol, cannabis, and cocaine abuse treatment clients and population controls.
A paucity of research exists on driving after use of cannabis or cocaine among clients in substance abuse treatment and changes in this behavior after treatment. The objectives of this research are to compare treatment clients and population controls before and after treatment in terms of: 1) amount of driving; 2) alcohol, cannabis, and cocaine consumption; 3) driving after use of alcohol, cannabis, and cocaine; and 4) driving infractions. Telephone interviews were conducted with a sample of 110 clients who received treatment in 1995 for a primary problem of alcohol (n = 44), cannabis (n = 37), or cocaine (n = 29) abuse. A random sample of 104 drivers from the general population, frequency matched by age and sex was also interviewed. Participants were asked to describe their driving habits and driving infractions before and after 1995. Both treatment and control groups reported about the same amount of driving. The treatment group reported significantly more consumption of alcohol, cannabis, and cocaine than did the control group before treatment. Significant declines in use for each substance were found for the treatment group after treatment, but use for the control group remained stable over the two time periods. Similarly significant declines in driving after use of alcohol, cannabis, and cocaine were found for the treatment group but the control group remained stable. Finally driving infractions, including speeding tickets, collisions, and license suspensions, significantly declined for the treatment group but not the control group. The results confirm that before treatment, the treatment subjects drove more frequently after consuming alcohol, cannabis, or cocaine than the control group. Declines in substance use and driving after treatment were accompanied by reductions in some types of driving infractions. Differences between groups, and over time in terms of driving while under the influence of psychoactive substances better explain the results than differences between groups in impulsivity/risk-taking or sleep problems.


Coupling field observations, soil modeling, and air dispersion algorithms to estimate 1,3-dichloropropene and chloropicrin flux and exposure.
Soil fumigants are volatile compounds applied to agricultural land to control nematode populations, weeds, and crop diseases. Field trials used for measuring fumigant loss from soil to the atmosphere encompass only a small proportion of the near semi-infinite parameter combinations of environmental, agronomic, and meteorological conditions. One approach to supplement field observations uses a soil physics model for fumigant emission predictions. A model is first validated against existing field study observations and then used to extrapolate results to a wider range of edaphic and climatic conditions. This work compares field observations of 1,3-dichloropropene and chloropicrin emissions to predictions from the USDA soil model CHAIN_2D. Comparison between model predictions and field observations for a Florida and California study had values between 0.62 to 0.81 and 0.99 to 1.0 for discrete and cumulative emission flux, respectively. CHAIN_2D emission rates were then coupled to several USEPA air dispersion models (ISCST3, CALPUFF6) to extend emission estimates to near field air concentrations. CALPUFF6 predicted slightly higher 1-h maximum air concentrations than ISCST3 for the same source strength (26.2-36.0% for setbacks between 1 and 250 m from the field edge, respectively). A sensitivity analysis for the CHAIN_2D/ISCST3 coupled numerical system is provided, with several soil and irrigation parameters consistently the most sensitive. Changes in the depth of incorporation, tarp material, and initial soil water content illustrate the predicted impact to emission strength and resulting near-field air concentrations with reductions of cumulative emission loss from 8.1 to 71% and average 1-h maximum air concentration reductions between 6.2 and 41% depending on the mitigation strategy chosen. Additionally, a stochastic framework based on the published SOFEA system that couples variability in experiment, model sensitivity, and site specific attributes is outlined should regional air concentration estimates resulting from fumigant use be sought.


[Respiratory and gastrointestinal symptoms in 7-10 year old children in Reykjavík, Iceland].
Asthma and rhinitis are common diseases in children often but not always caused by allergy. Gastroesophageal reflux is also prevalent in children and relationship with respiratory symptoms has been suggested. The aim of this study was to investigate this relationship in schoolchildren. As a part of multi-centre cross-sectional food allergy study (Europrevall), a short questionnaire was sent out to 2895 schoolchildren in Reykjavik 7-10 year old. Of the 2346 (81%) children we received answers from we selected those that answered positively to questions regarding common foods and a random sample of those who denied any symptoms related to food. The selected children were invited to further study where they answered an extensive questionnaire that included questions regarding respiratory and gastrointestinal symptoms. A significant correlation was found between a history of wheezing over the previous year and vomiting, (p<0.001) and feeling nauseous (p<0.001) in the past 6 months. There was also a correlation between asthma in the previous year and feeling nauseous (p<0.05), having a a burning or painful feeling in the middle of the chest (p<0.001) as well as nasal symptoms and vomiting (p<0.01), feeling nauseous (p<0.01), having a burning or painful feeling in the middle of the chest (p<0.01) and having a sour taste, like a taste of vomit in the mouth (p<0.001). This study shows a significant correlation between symptoms of gastroesophageal reflux and respiratory and nasal symptoms. Clinicians should be aware of this association though the nature and direction of this association is still unclear.


THE SEDIMENTATION PROPERTIES OF THE SKIN-SENSITIZING ANTIBODIES OF RAGWEED-SENSITIVE PATIENTS.
The sedimentation coefficients of the skin-sensitizing antibodies to ragweed were evaluated by the moving partition cell method and the sucrose density gradient method. The most reliable results were obtained by sucrose density gradient ultracentrifugation which showed that the major portion of skin-sensitizing antibodies to ragweed sediment with an average value of 7.7S (7.4 to 7.9S). This is about one S unit faster than gamma-globulins (6.8S). The data from the moving partition cell method are in agreement with these results. Our studies failed to demonstrate heterogeneity of the skin-sensitizing antibodies with regard to sedimentation rate.


The management of ductal carcinoma in situ (DCIS). The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Canadian Association of Radiation Oncologists.
To help physicians and patients arrive at the most clinically effective approach to the management of ductal carcinoma in situ (DCIS). Mastectomy, wide-excision breast-conserving surgery (BCS) plus radiotherapy and BCS alone. Overall survival, local recurrence, cosmesis, complications of therapy. Review of English language literature published between 1976 and December 1996; identified through MEDLINE. Nonsystematic review continued to July 1997. Also reviewed were reference lists of books and relevant articles. The first step in the diagnosis of DCIS, after history-taking and clinical examination, is a complete mammographic work-up. Once DCIS is suspected, either image-guided core biopsy or open surgical biopsy must be carried out. At surgical excision, the suspect area should be removed in 1 piece and a specimen radiograph obtained. Tissue should not be sent for frozen-section examination or hormone receptor analysis. The pathology report should address those features that bear on treatment choice. The specimen should, whenever possible, be reviewed by a pathologist experienced in breast disease. Treatment options for DCIS are mastectomy, wide-excision BCS plus radiotherapy or BCS alone. Treatment should aim to achieve a high degree of local control with the first treatment plan. Final decisions on treatment should not be made until the pathological findings have been reviewed and the specimen radiograph compared with the mammogram. Mastectomy is indicated when lesions are so large or diffuse that they cannot be completely removed without causing unacceptable cosmesis or when there is persistent involvement of the margins, especially with high-grade malignant lesions. Subcutaneous mastectomy should not be used to treat DCIS. Mastectomy should not be followed by adjuvant local radiotherapy or systemic therapy. Bilateral mastectomy is not normally indicated for patients with unilateral DCIS. BCS requires wide excision in patients with DCIS. It should be followed by mammography of the involved breast if the specimen radiograph does not clearly include all microcalcifications. BCS should normally be followed by radiotherapy. However, omission of radiotherapy may be considered when lesions are small and are low grade, and when pathological assessment shows clear margins. BCS should be accepted by patients only after they have received a careful explanation of the need for radiotherapy, its side effects and the associated logistic requirements. Axillary surgery, whether as a full or limited procedure, should not usually be performed in women with DCIS. Evidence is not available to support the use of tamoxifen in the treatment of women with DCIS. Patients should be offered the opportunity to participate in clinical trials whenever possible. Guidelines were reviewed and revised by the Writing Committee, expert primary reviewers, secondary reviewers selected from all regions of Canada and by the Steering Committee. The final document reflects a consensus of all these contributors.


[Serological survey of Toxoplasma gondii infection in isolated Amerindians, Mato Grosso].
This study determined the occurrence of the antibodies anti-Toxoplasma gondii among the Enawenê-Nawê, an indigenous population of Mato Grosso. These inhabit a vast wild area, with rare contacts with non-Indians. They do not keep domestic animals, including cats. Their diet is based on insects, cassava, corn, honey and mushrooms, they do not consume meat, except fish. Based on the above, serologic tests ELISA-IgG and indirect fluorescent antibody test for IgG/IgM were performed. From 148 samples, 80.4% positive for IgG by ELISA or indirect fluorescent antibody test. No IgM reagent cases were detected. In that group the seropositivity rates increased significantly with age from 50% to 95%. Having analyzed their customs and habits, together with the high seropositivity found, it is suggested that the presence of wild felines in the vicinity of the village and areas where water collects could play an important role as an infection source, contaminating soil and consequently insects and mushrooms consumed by the Indians.


The interaction of daunomycin with polydeoxynucleotides.
The ability of daunomycin to bind to various DNA polymers has been sutided by thermal denaturation, spectrophotometric analysis and inhibition of the polymerisation reactions catalysed by Escherichia coli DNA polymerase I and rat liver DNA polymerase alpha. The quantitative binding measurements revealed that the antibiotic binds tightly to all synthetic polydeoxynucleotides studied. The results demonstrated that daunomycin can bind with equal affinity to dG . dC or dA . dT basepaired sequences. However, the number of binding sites per nucleotide for poly(dA) . poly(dT) is significantly lower than that found for poly(dA-dT) . poly(dA-dT), thus indicating an appreciable preference of the drug for the alternating copolymer. The inactivation of the template properties of the synthetic DNA polymers in the DNA polymerase system is consistent with their daunomycin binding ability. However, a lack of correlation was observed between the drug binding ability of different DNA polymers and the binding-induced stabilisation of the double helix to heat denaturation.


Tractography Analysis of 5 White Matter Bundles and Their Clinical and Cognitive Correlates in Early-Course Schizophrenia.
Tractography is the most anatomically accurate method for delineating white matter tracts in the brain, yet few studies have examined multiple tracts using tractography in patients with schizophrenia (SCZ). We analyze 5 white matter connections important in the pathophysiology of SCZ: uncinate fasciculus, cingulum bundle (CB), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus, and arcuate fasciculus (AF). Additionally, we investigate the relationship between diffusion tensor imaging (DTI) markers and neuropsychological measures. High-resolution DTI data were acquired on a 3 Tesla scanner in 30 patients with early-course SCZ and 30 healthy controls (HC) from the Boston Center for Intervention Development and Applied Research study. After manually guided tracts delineation, fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD) were calculated and averaged along each tract. The association of DTI measures with the Scales for the Assessment of Negative and Positive Symptoms and neuropsychological measures was evaluated. Compared to HC, patients exhibited reduced FA and increased trace and RD in the right AF, CB, and ILF. A discriminant analysis showed the possible use of FA of these tracts for better future group membership classifications. FA and RD of the right ILF and AF were associated with positive symptoms while FA and RD of the right CB were associated with memory performance and processing speed. We observed white matter alterations in the right CB, ILF, and AF, possibly caused by myelin disruptions. The structural abnormalities interact with cognitive performance, and are linked to clinical symptoms.


A class I MHC-restricted recall response to a viral peptide is highly polyclonal despite stringent CDR3 selection: implications for establishing memory T cell repertoires in "real-world" conditions.
In this study, we analyze the recall response to influenza A matrix peptide M1(58-66) restricted by HLA-A2 in one individual and find a strict CDR3 selection as well as a high degree of polyclonality. The TCR beta-chain repertoire of memory T cells specific for this Ag system has been shown previously to be constrained by the use of the BV17 family and the I/sRS(A)/S amino acid motif in the CDR3 region. Our sequence analysis of BV17 TCR from a CTL line showed the repertoire to be highly polyclonal, as 95 distinct CDR3 sequences (clonotypes) were identified expressing this CDR3 motif. The clonotype frequencies showed a power law distribution with an extensive low-frequency tail. The clonotypes present in the high-frequency component of the distribution could be measured directly in the PBMC. This measurement showed that the relative frequencies of these clonotypes before stimulation were similar to their frequencies after culturing. Analysis of short-term cultures showed that the responding clonotypes have a similar ability to proliferate, which is independent of TCR beta-chain CDR3 sequence or precursor frequency. These data indicate that the memory T cell repertoire is composed of a surprisingly diverse set of T cell clonotypes with a limited potential for expansion. We propose that the high-frequency component represents T cells that have existed the longest. In keeping with this hypothesis, these clonotypes were measured over a 2-year period, during which their precursor frequency did not change.


Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate.
Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet been studied in HNSCC. To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia. This was an observational study (including sensitivity and specificity analysis) of BLZ-100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen-induced dysplasia model of hamster cheek pouches. Various HNSCC xenografts were established in the tongues of NOD-scid IL2Rgammanull (NSG) mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the cheek pouch of Golden Syrian hamsters for 9 to16 weeks. BLZ-100 was subcutaneously injected, and fluorescence uptake was measured. The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades. In HNSCC xenografts, BLZ-100 demonstrated a mean (SD) SBR of 2.51 (0.47). The ROC curve demonstrated an area under the curve (AUC) of 0.89; an SBR of 2.50 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and nontumor interface, the AUC increased to 0.97; an SBR of 2.50 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades of dysplasia. The SBR of high-grade dysplasia was significantly greater than that of mild-to-moderate dysplasia (2.31 [0.71] vs 1.51 [0.34], P = .006). BLZ-100 is a sensitive and specific marker of HNSCC and can distinguish high-risk from low-risk dysplasia. BLZ-100 has the potential to serve as an intraoperative guide for tumor margin excision and identification of premalignant lesions.


Extracellular vesicle concentration and procoagulant activity of canine haemoperitoneum fluid and packed red blood cells.
To compare the concentration of phosphatidylserine-positive extracellular vesicles and phosphatidylserine-derived procoagulant activity of canine haemoperitoneum fluids and packed red blood cell units. Ten dogs with haemoperitoneum (neoplasia = 7; trauma = 1; other = 2) were recruited, and five non-leukoreduced packed red blood cell units purchased. Supernatants were collected from haemoperitoneum samples and packed red blood cell units using a consistent centrifugation protocol. Phosphatidylserine-positive extracellular vesicle concentrations were measured by flow cytometry and phosphatidylserine-mediated procoagulant activity by a commercial thrombin generation assay. Phosphatidylserine-mediated procoagulant activity was significantly higher for supernatants collected from packed red blood cell units (median 54 nM, range 53 to 60 nM) than haemoperitoneum samples (median 43 nM; range 7 to 51 nM; P = 0.0007). By flow cytometry, the concentration of phosphatidylserine-positive extracellular vesicles was not significantly different between packed red blood cell (median: 415/μL, range 173 to 1331/μL) and haemoperitoneum samples (median: 314/μL, range 132 to 3880/μL; P = 0.77). This study does not suggest that shed abdominal blood contains more extracellular vesicles with phosphatidylserine-mediated procoagulant activity than donor packed red blood cell units. Clinical studies to compare the effects of autologous transfusion of shed abdominal blood and packed red blood cell units on coagulation status and clinical outcome are required.


Grasping detection of dual manipulators based on Markov decision process with neural network.
With the development of artificial intelligence, robots are widely used in various fields, grasping detection has been the focus of intelligent robot research. A dual manipulator grasping detection model based on Markov decision process is proposed to realize the stable grasping with complex multiple objects in this paper. Based on the principle of Markov decision process, the cross entropy convolutional neural network and full convolutional neural network are used to parameterize the grasping detection model of dual manipulators which are two-finger manipulator and vacuum sucker manipulator for multi-objective unknown objects. The data set generated in the simulated environment is used to train the two grasping detection networks. By comparing the grasping quality of the detection network output the best grasping by the two grasping methods, the network with better detection effect corresponding to the two grasping methods of two-finger and vacuum sucker is determined, and the dual manipulator grasping detection model is constructed in this paper. Robot grasping experiments are carried out, and the experimental results show that the proposed dual manipulator grasping detection method achieves 90.6% success rate, which is much higher than the other groups of experiments. The feasibility and superiority of the dual manipulator grasping detection method based on Markov decision process are verified.


Limited proteolysis as a probe of the conformation and nucleic acid binding regions of nucleolin.
Nucleolin, also called protein C23, is a RNA-associated protein implicated in the early stages of ribosome assembly. To study the general conformation and map the nucleic acid binding regions, rat nucleolin was subjected to limited proteolysis using trypsin and chymotrypsin in the presence or absence of poly(G). The cleavage sites were classified according to their locations in the three putative domains: the highly polar amino-terminal domain, the central nucleic acid binding domain, which contains four 90-residue repeats, and the carboxyl-terminal domain, which is rich is glycine, dimethylarginine, and phenylalanine. The most labile sites were found in basic segments of the amino-terminal domain. This region was stabilized by Mg2+. At low enzyme concentrations, cleavage by trypsin or chymotrypsin in the amino-terminal domain was enhanced by poly(G). Trypsin produced a relatively stable 48-kDa fragment containing the central and carboxyl-terminal domains. The enhanced cleavage suggests that binding of nucleic acid by the central domain alters the conformation of the amino-terminal domain, exposing sites to proteolytic cleavage. At moderate enzyme concentrations, the 48-kDa fragment was protected by poly(G) against tryptic digestion. At the highest enzyme concentrations, both enzymes cleaved near the boundaries between repeats 2, 3, and 4 with some sites protected by poly(G), suggesting that the repeats themselves form compact units. The carboxyl-terminal domain was resistant to trypsin but was cleaved by chymotrypsin either in the presence or in the absence of poly(G), indicating exposure of some phenylalanines in this region. These studies provide a general picture of the topology of nucleolin and suggest that the nucleic acid binding region communicates with the amino-terminal domain.


A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates.
The development of a safe and effective mucosal adjuvant is a crucial step toward a mucosal HIV/AIDS vaccine. This study seeks to determine the promise of a nontoxic mutant of cholera toxin (mCT; E112K) as a mucosal adjuvant in nonhuman primates. HIV-1 gp120 was nasally administered together with mCT E112K or native CT (nCT) as adjuvant on five to six occasions over a 6- to 8-wk period to groups of four rhesus macaques and alone to two monkeys that acted as controls. Macaques given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG and IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues and of IL-4-producing Th2-type CD4-positive (CD4(+)) T cells than did controls. Even though significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal damage was observed only in the nCT-treated, but not in the control or mCT E112K-treated groups. These results clearly show that mCT E112K is an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.


To search or to like: Mapping fixations to differentiate two forms of incidental scene memory.
We employed eye-tracking to investigate how performing different tasks on scenes (e.g., intentionally memorizing them, searching for an object, evaluating aesthetic preference) can affect eye movements during encoding and subsequent scene memory. We found that scene memorability decreased after visual search (one incidental encoding task) compared to intentional memorization, and that preference evaluation (another incidental encoding task) produced better memory, similar to the incidental memory boost previously observed for words and faces. By analyzing fixation maps, we found that although fixation map similarity could explain how eye movements during visual search impairs incidental scene memory, it could not explain the incidental memory boost from aesthetic preference evaluation, implying that implicit mechanisms were at play. We conclude that not all incidental encoding tasks should be taken to be similar, as different mechanisms (e.g., explicit or implicit) lead to memory enhancements or decrements for different incidental encoding tasks.


Beliefs about hypnosis: popular beliefs, misconceptions, and the importance of experience.
Contemporary views and opinions about hypnosis were sampled with a modified version of McConkey's Opinions About Hypnosis (OAH) scale. The OAH was administered at 2 different times, 1 month apart, to 276 undergraduate students. Approximately half of the participants completed the Harvard Group Scale of Hypnotic Susceptibility, Form A, between the survey sessions. Results indicated that the experience of being hypnotized modified a majority of the opinions sampled, with participants expressing less stereotypic views about hypnosis after being hypnotized. Expressed opinions and beliefs about hypnosis failed to meaningfully correlate with hypnotizability scores.


Enzyme-linked immunosorbent assay for diagnosis of chronic Q fever.
From 1982 through 1987 we diagnosed 13 chronic Q fever cases. Clinically these patients presented a culture-negative endocarditis, and all but two had high complement-fixing antibody titers to Coxiella burnetii phase I (reciprocal titer above 200). With the enzyme-linked immunosorbent assay (ELISA), titers of immunoglobulin G (IgG) to phases I and II of C. burnetii averaged 158,000 and 69,900, respectively, whereas they reached 300 and 3,200 in acute Q fever cases. Similarly, IgA to both phases of C. burnetii and IgM to phase I were consistently higher during chronic than acute Q fever. The serological follow-up of one patient with chronic Q fever over a 4-year period showed a good correlation between the titers of IgG and IgM antibody titers detected by ELISA and indirect fluorescent-antibody test (IFA) to both phases of C. burnetii. Few discrepancies appeared with IgA. Shortly after initiation of antibiotic treatment, a slow and steady decrease of the antibody titers to C. burnetii phases I and II was observed. The complement fixation, IFA, and ELISA tests showed the same type of antibody response. The ELISA proved to be an excellent diagnostic test for chronic Q fever. It distinguished negative from positive reactions clearly, and results were highly reproducible. The reading is objective, and the test is simple to perform and more sensitive than the IFA and complement fixation tests. The ELISA is recommended for serologic evaluation of patients with chronic Q fever.


The clinical setting and pharmacology of intraperitoneal chemotherapy: an overview.
Intraperitoneal chemotherapy first arose in response to unrelated studies introducing such concepts as the presence of a peritoneal diffusion barrier that acted to slow the systemic release of the drug and the incidence of small miliary nodules remaining on the peritoneal surface after initial clinical response. These minimum residual disease patients were considered the best clinical group for early study of intraperitoneal therapy. The problem of access to the peritoneal cavity was solved with the Tenckhoff catheter, which had previously been used for whole peritoneal dialysis in nephrology patients. There was also some concern about drug distribution, but a radiologic visualization technique was developed that revealed distribution to be satisfactory in most patients. Systemic delivery of the study drug was not shown to be compromised by intraperitoneal administration of 5-fluorouracil, an agent that has advantageous activity for ovarian cancer therapy. Cisplatin, however, was generally considered the most efficacious drug for treatment of this disease, although it has not yet been extensively studied. Intraperitoneal chemotherapy is currently attracting a great deal of attention, and its potential applications are many.


Evidence-based use of second-generation antipsychotics in a state Medicaid pediatric population, 2001-2005.
The purpose of this study was to identify children in a state Medicaid population who were newly treated with second-generation antipsychotics from 2001 through 2005, to classify each use of these agents as evidence based or not depending on the child's diagnoses, and to identify factors associated with the likelihood of evidence-based use of the medication. A Medicaid claims database was used to retrospectively identify enrollees receiving initial outpatient treatment with a second-generation antipsychotic between 2001 and 2005. To capture all relevant treatments and diagnoses, claims were examined from January 2000 through December 2006. The final sample included 11,700 children under age 18. The primary measure of interest was the proportion for whom use of the antipsychotic was based on evidence. Evidence-based use (categorized as strong, plausible, or weak evidence) was defined as any use of the agent for a diagnosis supported by a clinical trial published before the end of 2005. Trend analysis and logistic regression were used. The number of children newly treated with second-generation antipsychotics increased from 1,482 in 2001 to 3,110 in 2005. Of the new users of these agents during the study period, 41.3% had no diagnosis for which such treatment was supported by a published study. The medication with the highest level of non-evidence-based use was aripiprazole (77.1%), and risperidone had the lowest (30.6%). The number of children receiving second-generation antipsychotics doubled in this Medicaid population between 2001 and 2005, and a large proportion of the treatments were not supported by evidence from clinical studies.


Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase.
The structure and function of microtubules (MTs) are regulated by post-translational modifications of tubulin subunits, such as acetylation of the Lys40 residue of α-tubulin. Regulation of the organization and dynamics of MTs is essential for the precise formation of the mitotic spindle. Spindle MTs are highly acetylated, but the mechanism regulating this acetylation is largely unknown. Furry (Fry) is an evolutionarily conserved protein that binds to MTs and colocalizes with acetylated MTs in the mitotic spindle. In this study, we examined the role of Fry in the acetylation of MTs in the mitotic spindle. Depletion of Fry significantly reduced the level of MT acetylation in the mitotic spindle. Expression of the N-terminal fragment of Fry induced hyperacetylation of MTs in both mitotic and interphase cells. These results indicate that Fry promotes MT acetylation in the mitotic spindle. We also found that Fry binds to the tubulin deacetylase SIRT2, preferentially in mitotic cells. Cell-free experiments revealed that the N-terminal region of Fry is the domain responsible for binding to and inhibiting the tubulin-deacetylase activity of SIRT2. AGK2, a specific inhibitor of SIRT2, increased the level of MT acetylation in the mitotic spindle, indicating that SIRT2 is involved in the deacetylation of spindle MTs. Furthermore, AGK2 reversed the decrease in MT acetylation induced by Fry depletion. In summary, these results suggest that Fry plays a crucial role in promoting the level of MT acetylation in the mitotic spindle by inhibiting the tubulin-deacetylase activity of SIRT2.


A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins.
We describe a method for assaying protein interactions that offers some attractive advantages over previous assays. This method, called bioluminescence resonance energy transfer (BRET), uses a bioluminescent luciferase that is genetically fused to one candidate protein, and a green fluorescent protein mutant fused to another protein of interest. Interactions between the two fusion proteins can bring the luciferase and green fluorescent protein close enough for resonance energy transfer to occur, thus changing the color of the bioluminescent emission. By using proteins encoded by circadian (daily) clock genes from cyanobacteria, we use the BRET technique to demonstrate that the clock protein KaiB interacts to form homodimers. BRET should be particularly useful for testing protein interactions within native cells, especially with integral membrane proteins or proteins targeted to specific organelles.


Medical Imaging for Improved Tumour Characterization, Delineation and Treatment Verification.
In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials were described by an expert group for each of nine major areas of radiation therapy research. This report deals with medical imaging for improved medical diagnosis including tumour detection, staging and characterization, treatment planning, guiding and verification, evaluation of response and treatment follow-up.


Human parvovirus B19 infection in a renal transplant recipient: a case report.
Parvovirus B19 presents tropism for human erythroid progenitor cells, causing chronic anemia in organ transplant recipients, due to their suppressed humoral and cellular responses. Diagnosis may be achieved through serological tests for detection of anti-B19 antibodies. However, renal transplant recipients are not routinely tested for parvovirus B19 infection, since there is scanty data or consensus on screening for B19 infection, as well as for treatment or preventive management of transplanted patients. Herein we report a kidney transplant recipient, who was unresponsive to treatment of severe anemia, and presented hypocellular hematopoietic marrow, megaloblastosis and hypoplasia of erythroid lineage with larger cells with clear nuclei chromatin and eosinophilic nuclear inclusions. This patient was seropositive for Epstein-Barr and Cytomegalovirus infections and negative for anti-parvovirus B19 IgM and IgG antibodies, although symptoms were suggestive of parvoviruses infection. A qualitative polymerase chain reaction testing for B19 in serum sample revealed positive results for B19 virus DNA. This case report suggests that the diagnostic process for parvovirus B19 in renal transplant recipients should include a polymerase chain reaction assay to detect B19-DNA, since specific serological tests may be unreliable given their impaired humoral responses. These results also indicate the importance of considering parvovirus B19 infection in the differential diagnosis of persistent anemia in transplanted patients.


Interaction of DGAT1 polymorphism, parity, and acetate supplementation on feeding behavior, milk synthesis, and plasma metabolites.
Acetate supplementation increases milk fat production, but interactions with animal-related factors have not been investigated. The objective of this study was to characterize the interaction of acetate supplementation with parity and genetic potential for milk fat synthesis including the DGAT1 K232A polymorphism (AA and KA genotypes). In total, 47 primiparous and 49 multiparous lactating cows were used in 2 blocks in a crossover design. The basal diet was formulated to have a low risk of biohydrogenation-induced milk fat depression and had 32.8% and 32.0% neutral detergent fiber and 21.7% and 23.6% starch [all on a dry matter (DM) basis] in block 1 and 2, respectively. The control treatment received the basal diet, and the acetate supplementation treatment included anhydrous sodium acetate supplemented to the basal diet at 3.2% and 3.1% of DM of the diet for block 1 and 2, respectively (targeting 10 mol/d of acetate). The DGAT1 genotype frequency of the experimental cows was 45% AA and 51% KA, with 4% cows with either a KK or unimputable genotype. Acetate supplementation increased DM intake (DMI) in KA multiparous cows, but acetate did not change DMI in AA multiparous or primiparous cows of either genotype. Acetate supplementation increased the frequency of meals by 8% and decreased the length of each meal by ∼5 min compared with control. There was no effect of acetate on milk yield. Acetate supplementation increased milk fat yield and concentration by 117 g/d and 0.31 percentage units, respectively, regardless of DGAT1 polymorphism or parity. The increase in milk fat yield was mostly due to an increase in yield of 16C mixed-sourced fatty acids, suggesting that acetate supplementation drives mammary de novo synthesis toward completion. Response to acetate supplementation was not related to genomic predicted transmitting ability of milk fat concentration and yield or to pretrial milk fat percent and yield, suggesting that acetate increases milk fat production regardless of genetic potential for milk fat yield and level of milk fat synthesis. Interestingly, analyzing the temporal effect on the interaction between treatment and DGAT1 polymorphism on milk fat yield suggested that DGAT1 polymorphism may affect the short-term response to acetate supplementation during the first ≤7 d on treatment. Acetate supplementation also increased plasma β-hydroxybutyrate concentration and decreased plasma glucose concentration. In conclusion, acetate supplementation consistently increased milk fat synthesis regardless of parity or genetic potential for milk fat synthesis.


Molecular Analysis of Evolution and Origins of Cultivated Hawthorn (Crataegus spp.) and Related Species in China.
Hawthorn is of high economic value owing to its medicinal properties and health benefits. Crataegus is a member of the Rosaceae family; the genus has a complicated taxonomic history, and several theories on its origin have been proposed. In this study, 53 accessions from seven Crataegus taxa native to China and accessions of exotic Crataegus species (two from Europe and one from North America) were analyzed by specific locus amplified fragment sequencing (SLAF-seq). In total, 933,450 single-nucleotide polymorphisms were identified after filtering and used to investigate the species' genomic evolution. Phylogenetic trees derived from nuclear simple sequence repeats (SSRs) and SLAF-seq data showed the same topology, in which Crataegus maximowiczii and Crataegus sanguineae formed a closely related cluster that was clearly separated from the cluster composed of Crataegus hupehensis, Crataegus pinnatifida, Crataegus pinnatifida var. major, Crataegus bretschneideri and Crataegus scabrifolia. Phylogenetic and structure analysis indicated that the seven Chinese Crataegus taxa had two separate speciation events. Plants that evolved the southwestern route shared the genepool with the European species, whereas plants along the northeastern route shared the genepool with the North American species. TreeMix genetic analysis revealed that C. bretschneideri may have a hybrid origin. This study provides valuable information on the origins of Chinese Crataegus and suggests an evolutionary model for the main Crataegus species that native to China.


Virtues in action - the new look of character traits.
The present study aimed to take fresh look at the nature and psychological meaning of consistency in character traits and virtuous behaviour as manifested in everyday life. To this end, a 10-day experience-sampling study was conducted. Using smartphone technology, a sample of 83 working mothers and fathers provided a total of 4,342 momentary behavioural reports while being in the role of the parent versus being in the job role. Consistent with recent research on personality traits, the findings of the present study showed that people express a wide range of virtue states in their everyday lives. Within-person changes in virtue states were not random but were contingent on people's current role context and also meaningfully related to their momentary affective experiences. At the same time, people's average level of virtue states, their degree of variation in virtue states, and their signature ways of reacting to role contexts turned out to be stable, trait-like individual difference characteristics. Discussion focuses on the implications for the conception of character traits in scientific psychology and beyond.


Pregnancies in young adolescent mothers: a population-based study on 37 million births.
Pregnancy in young adolescents is often understudied. The objective of our study was to evaluate the effect of young maternal age on adverse obstetrical and neonatal outcomes. We conducted a population-based cohort study using the Center for Disease Control and Prevention's Linked Birth-Infant Death and Fetal Death data on all births in the US between 1995 and 2004. We excluded all births of gestational age under 24 weeks and those with reported congenital malformations or chromosomal abnormalities. Maternal age was obtained from the birth certificate and relative risks estimating its effect on obstetrical and neonatal outcomes were computed using unconditional logistic regression analysis. 37,504,230 births met study criteria of which 300,627 were in women aged <15 years with decreasing rates from 11/1,000 to 6/1,000 over a 10-year period. As compared to women 15 years and older, women <15 were more likely to be black and Hispanic, less likely to have adequate prenatal care, and more likely to not have had any prenatal care. In adjusted analysis, births to women <15 were more likely to be IUGR, born under 28, 32, and 37 weeks' gestation and to result in stillbirths and infant deaths. Prenatal care was protective against infant deaths in women < 15 years of age. Although public health initiatives have been successful in decreasing rates of young adolescent pregnancies, these remain high risk pregnancies that may benefit from centers capable of ensuring adequate prenatal care.


Geometry, features, and panoramic views: ants in rectangular arenas.
When tested in rectangular arenas, the navigational behavior of the ant Gigantiops destructor can produce results similar to vertebrates. Such results are usually interpreted as supporting the ability of animals to segregate spatial geometry and features. Here, we combine a detailed analysis of ants' paths with panoramic images taken from the ant's perspective that can serve as a basis for developing view-based matching models. The corner choices observed in ants were better predicted by the use of panoramic views along with a simple matching process [rotational image difference function (rIDF)] than by models assuming segregation of geometry and features (G/F). Our view-based matching model could also explain some aspects of the ants' path (i.e., initial direction, length) resulting from the different visual conditions, suggesting that ants were using such a taxon-like strategy. Analyzed at the individual level, the results show that ants' idiosyncratic paths tend to evolve gradually from trial to trial, revealing that the ants were partially updating their route memory after each trial. This study illustrates the remarkable flexibilities that can arise from the use of taxon-like strategies and stresses the importance of considering them in vertebrates.


Partial gonadal dysgenesis in a patient with a marker Y chromosome.
We evaluated a patient with partial gonadal dysgenesis including a right dysgenetic testis and a left streak gonad with rudimentary fallopian tube and uterus. She had ambiguous external genitalia and was raised female. Although her height is normal (25th centile at age 12 years), she has some findings of Ullrich-Turner syndrome. Her karyotype was reported to be 46,X,+marker; subsequent molecular investigations showed the marker to be the short arm of the Y chromosome. Genomic DNA, isolated from leukocytes of the patient and her father, was digested with a variety of restriction endonucleases and subjected to Southern blot analysis. A positive hybridization signal was obtained with probes for the short arm of the Y chromosome (pRsY0.55, SRY, ZFY, 47Z, pY-190, and YC-2) in DNA from the patient, indicating the presence of most if not all of the short arm, while long arm probes (HinfA and pY3.4) indicated that at least 75% of the long arm of the Y chromosome was missing. The gene responsible for testicular determination (TDF) is on the distal portion of the short arm of the Y chromosome; Yq has no known influence on sex determination. Hence, the deletion of the long arm of the Y chromosome cannot explain the gonadal dysgenesis in this patient. One explanation for the gonadal dysgenesis and Ullrich-Turner phenotype in the patient could be undetected 45,X/46,X,+marY mosaicism but no such mosaicism was observed in peripheral lymphocytes. Several investigators have suggested the presence of an "anti-Turner" gene near TDF. Hence it is possible that the clinical phenotype in our patient results from a Y chromosomal defect in sequences flanking TDF, which reduces the function of both TDF and the "anti-Turner" genes.


In search of sports biomechanics' holy grail: Can athlete-specific optimum sports techniques be identified?
The development of methods that can identify athlete-specific optimum sports techniques-arguably the holy grail of sports biomechanics-is one of the greatest challenges for researchers in the field. This 'perspectives article' critically examines, from a dynamical systems theoretical standpoint, the claim that athlete-specific optimum sports techniques can be identified through biomechanical optimisation modelling. To identify athlete-specific optimum sports techniques, dynamical systems theory suggests that a representative set of organismic constraints, along with their non-linear characteristics, needs to be identified and incorporated into the mathematical model of the athlete. However, whether the athlete will be able to adopt, and reliably reproduce, his/her predicted optimum technique will largely be dependent on his/her intrinsic dynamics. If the attractor valley corresponding to the existing technique is deep, or if the attractor valleys corresponding to the existing technique and the predicted optimum technique are in different topographical regions of the dynamic landscape, technical modifications may be challenging or impossible to reliably implement even after extended practice. The attractor layout defining the intrinsic dynamics of the athlete, therefore, needs to be determined to establish the likelihood of the predicted optimum technique being reliably attainable by the athlete. Given the limited set of organismic constraints typically used in mathematical models of athletes, combined with the methodological challenges associated with mapping the attractor layout of an athlete, it seems unlikely that athlete-specific optimum sports techniques will be identifiable through biomechanical optimisation modelling for the majority of sports skills in the near future.


Adult neuroplasticity: more than 40 years of research.
Within the last four decades, our view of the mature vertebrate brain has changed significantly. Today it is generally accepted that the adult brain is far from being fixed. A number of factors such as stress, adrenal and gonadal hormones, neurotransmitters, growth factors, certain drugs, environmental stimulation, learning, and aging change neuronal structures and functions. The processes that these factors may induce are morphological alterations in brain areas, changes in neuron morphology, network alterations including changes in neuronal connectivity, the generation of new neurons (neurogenesis), and neurobiochemical changes. Here we review several aspects of neuroplasticity and discuss the functional implications of the neuroplastic capacities of the adult and differentiated brain with reference to the history of their discovery.


Predictors of hepatitis C treatment response: what's new?
Hepatitis C virus infection is a growing, global health problem, with mortality expected to reach a peak in the next ten years in many western countries. A number of host and viral factors have been established as useful predictors of treatment response in the context of interferon and ribavirin. Several new markers have recently been identified that improve our understanding of treatment response. The addition of protease inhibitors to treatment regimens has highlighted the importance of viral kinetics on-treatment in predicting response to treatment. Many new classes of direct acting anti-virals are currently being developed and expected to be clinically available in the near future. Current predictors of treatment response will be redefined in the context of interferon free regimens.


The Relationship Between Autonomic Dysfunction of the Gastrointestinal Tract and Emotional Distress in Patients With Systemic Sclerosis.
We hypothesized that emotional distress in systemic sclerosis (SSc) patients with moderate to severe gastrointestinal (GI) dysfunction is associated with dysautonomia. We sought to determine (1) the clinical characteristics associated with emotional distress in SSc, (2) the odds of having dysautonomia in those with emotional distress, and (3) whether GI dysautonomia, as measured by the Survey of Autonomic Symptoms (SAS), correlates with GI dysautonomia on the Composite Autonomic Symptom Score-31 (COMPASS-31). Clinical and demographic features from our prospective cohort study were compared among SSc patients with and without GI-associated emotional distress (University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 well-being subscale >0.5 or ≤0.5) in cross-sectional analysis. Covariates/confounders independently associated with emotional distress were used to construct multivariable logistic regression models. The COMPASS-31 and SAS GI subdomains were compared with Spearman correlation. Forty-six patients with SSc were enrolled in the study. In univariate analyses, age (odds ratio [OR], 1.06; p = 0.026), severity of GI dysautonomia (COMPASS-31: OR, 1.41; p = 0.003), anti-centromere (A/B) antibodies (OR, 3.60; p = 0.044), and anti-PM-Scl (75/100) antibodies (OR, 0.15; p = 0.035) were associated with emotional distress. In the adjusted model, those with more severe GI dysautonomia remained more likely to have emotional distress (OR, 1.85; p = 0.026); those with anti-PM-Scl (75/100) antibodies were less likely to have emotional distress (OR, 0.03; p = 0.031). The SAS and COMPASS-31 GI subdomains moderately correlated (ρ = 0.68, p < 0.001). In SSc, increased symptom burden related to GI dysautonomia is associated with emotional distress. Multidisciplinary approaches addressing both the physical and emotional needs of the SSc patient may be warranted to optimize patient care.


[The influence of calcium ion antagonists on the effects of bradykinin].
On the isolated segments of the ileum of the guinea-pig, anesthetized and nonanesthetized rats and mice it was established that calcium ion antagonists from different chemical series exert the nonspecific antibradykinin action, reducing the main biological effects of bradykinin--myotropic, depressor, nociceptive and microcirculatory. To a greater extent the mentioned properties show up in the derivatives of 1,4-dihydropyridine (phoridon, etc.) that may play the certain role in the therapeutic action of the drugs in the diseases associated with the activation of the kinin system of the organism.


Tumor induction by murine sarcoma virus in AKR and C58 mice. Reduction of tumor regression associated with appearance of Gross leukemia virus pseudotypes.
Adult AKR and C58 mice injected intramuscularly with murine sarcoma virus, Moloney isolate (M-MSV), developed high incidence of nonregressing local tumors. Histologically, these tumors revealed the typical pleomorphism of M-MSV sarcomas; in some cases, however, neoplastic tissue showed a nodular or diffuse growth of monomorphic myoblastlike cells, reminiscent of clonal aggregates. No depression of immune reactivity was found in M-MSV-injected mice as evaluated by direct hemolytic plaque-forming cells against SRBC and by virus-neutralizing antibody production. The MSV recovered from the induced tumors proved to be, by neutralization assay, a Gross (G)-MSV pseudotype. Moreover, tumor cell suspensions absorbed out cytotoxic antibody directed against G-cell surface antigens. Therefore, the conclusion was drawn that MSV with envelope characteristics of endogenous G leukemia virus had formed in vivo through a phenotypic mixing phenomenon. The failure of tumors to regress has been interpreted as mainly due to the partial unresponsiveness of host immune reactivity towards G-MuLV specified antigens. Since MSV-tumors arose in AKR mice after a very long latent period, the possibility was considered that this relative resistance might depend on immunologic mechanisms. In fact, M-MSV-injected AKR mice immunodepressed by goat antimouse lymphocyte serum or rendered partially tolerant by neonatal M-MuLV inoculation developed sarcomas with higher incidence and with a shorter latency. Furthermore, the MSV recovered from these early tumors proved to be the original Moloney pseudotype.


Contraception after Abortion and Risk of Repeated Unintended Pregnancy among Health Plan Members.
Optimizing access to effective contraception at the time of abortion can reduce repeated unintended pregnancies. To assess contraception initiation and repeated unintended pregnancies among women receiving abortions in Kaiser Permanente Northern California (KPNC) facilities and through outside contracted facilities. A retrospective cohort study was conducted using a randomized proportional sample of women aged 15 to 44 years having abortions in KPNC, to determine contraception initiation within 90 days. Demographic and clinical characteristics (age, race/ethnicity, gravidity, parity, contraceptive method initiated, and pregnancies within 12 months) were collected from electronic health records. Descriptive statistics, χ2 tests, t-tests, and logistic regression models assessed predictors of long-acting reversible contraception (LARC) initiation and having another unintended pregnancy within 12 months of abortion. Women having abortions from contracted facilities were significantly less likely to initiate LARC within 90 days compared with those receiving abortions in KPNC facilities (11.99% vs 19.10%, p = 0.012). Significant factors associated with 90-day LARC initiation included abortions in KPNC facilities (adjusted odds ratio [aOR] = 1.87, p = 0.007) and gravidity of 3 or more. Women initiating short-acting or no contraception were significantly more likely to have an unintended pregnancy within 12 months of the abortion than those initiating LARC (aOR = 3.66, p = 0.005; no contraception vs LARC, aOR = 3.75, p = 0.005). In response to this study, KPNC now provides reimbursement for LARC in all outside abortion contracts, internalized more abortions in KPNC facilities, and strengthened clinical recommendations for immediate, effective postabortion contraception, especially LARC.


α2- and β2-Adrenoreceptor-Mediated Efficacy of the Atypical Antidepressant Agomelatine Combined With Gabapentin to Suppress Allodynia in Neuropathic Rats With Ligated Infraorbital or Sciatic Nerve.
Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves has specific characteristics and responds differently to alleviating drugs at cephalic versus extracephalic level. This is especially true for tricyclic antidepressants currently used for alleviating neuropathic pain in humans which are less effective against cephalic neuropathic pain. Whether this also applies to the antidepressant agomelatine, with its unique pharmacological properties as MT1/MT2 melatonin receptor agonist and 5-HT2B/5-HT2C serotonin receptor antagonist, has been investigated in two rat models of neuropathic pain. Acute treatments were performed 2 weeks after unilateral chronic constriction (ligation) injury to the sciatic nerve (CCI-SN) or the infraorbital nerve (CCI-ION), when maximal mechanical allodynia had developed in ipsilateral hindpaw or vibrissal pad, respectively, in Sprague-Dawley male rats. Although agomelatine (45 mg/kg i.p.) alone was inactive, co-treatment with gabapentin, at an essentially ineffective dose (50 mg/kg i.p.) on its own, produced marked anti-allodynic effects, especially in CCI-ION rats. In both CCI-SN and CCI-ION models, suppression of mechanical allodynia by 'agomelatine + gabapentin' could be partially mimicked by the combination of 5-HT2C antagonist (SB 242084) + gabapentin, but not by melatonin or 5-HT2B antagonist (RS 127445, LY 266097), alone or combined with gabapentin. In contrast, pretreatment by idazoxan, propranolol or the β2 antagonist ICI 118551 markedly inhibited the anti-allodynic effect of 'agomelatine + gabapentin' in both CCI-SN and CCI-ION rats, whereas pretreatment by the MT1/MT2 receptor antagonist S22153 was inactive. Altogether these data indicate that 'agomelatine + gabapentin' is a potent anti-allodynic combination at both cephalic and extra-cephalic levels, whose action implicates α2- and β2-adrenoreceptor-mediated noradrenergic neurotransmission.


Percutaneous angioplasty in the treatment of thrombosed hemodialysis fistulas: A single-center experience with 1 year of follow-up.
Thrombosis of a hemodialysis arteriovenous fistula (AVF) is a serious complication that needs urgent treatment. Most cases are treated surgically, but recently, endovascular strategies have become a viable alternative. This study is an evaluation of the success and patency rate of percutaneous balloon angioplasty of thrombosed hemodialysis fistulas using a drug-coated balloon (DCB) contrasted with a standard balloon (SB). The data of 33 patients with a thrombosed native hemodialysis AVF treated percutaneously in a tertiary care center were analyzed retrospectively. Success of the procedure was defined as restoration of flow with less than 30% residual stenosis and resumption of dialysis through the hemodialysis AVF. The success rate of the procedure and the patency rate at 1, 6, and 12 months were evaluated. The effect on patency of a DCB was compared to that of a SB. Twenty-five radiocephalic and 8 brachiocephalic thrombosed hemodialysis AVFs were treated during the study period. Flow was restored in 23 thrombosed fistulas, a success rate of 69.7%. The patency rate of successfully treated fistulas was 95.6% at 1 month, 76.1% at 6 months, and 57.9% at 12 months. Ten of the 23 re-established AVFs were treated with a DCB and the remainder were treated with a SB. The patency of the fistulas treated with a DCB was similar to that of a SB at 1 month (100% vs 92.3%, respectively; p=0.393). The patency rate of a DCB was greater than that of a SB at 6 months (88.9% vs 66.7%, respectively; p=0.258) and 12 months (75% vs 45.4%, respectively; p=0.219). Percutaneous intervention for thrombosed hemodialysis AVFs is a safe, minimally invasive, and effective procedure. There was a positive trend in the patency rate of patients treated with a DCB at 6 and 12 months compared with a SB.


The emerging roles of phosphatases in Hedgehog pathway.
Hedgehog signaling is evolutionarily conserved and plays a pivotal role in cell fate determination, embryonic development, and tissue renewal. As aberrant Hedgehog signaling is tightly associated with a broad range of human diseases, its activities must be precisely controlled. It has been known that several core components of Hedgehog pathway undergo reversible phosphorylations mediated by protein kinases and phosphatases, which acts as an effective regulatory mechanism to modulate Hedgehog signal activities. In contrast to kinases that have been extensively studied in these phosphorylation events, phosphatases were thought to function in an unspecific manner, thus obtained much less emphasis in the past. However, in recent years, increasing evidence has implicated that phosphatases play crucial and specific roles in the context of developmental signaling, including Hedgehog signaling. In this review, we present a summary of current progress on phosphatase studies in Hedgehog pathway, emphasizing the multiple employments of protein serine/threonine phosphatases during the transduction of morphogenic Hedgehog signal in both Drosophila and vertebrate systems, all of which provide insights into the importance of phosphatases in the specific regulation of Hedgehog signaling.


FKBP51 controls cellular adipogenesis through p38 kinase-mediated phosphorylation of GRα and PPARγ.
Glucocorticoid receptor-α (GRα) and peroxisome proliferator-activated receptor-γ (PPARγ) are critical regulators of adipogenic responses. We have shown that FK506-binding protein 51 (FKBP51) represses the Akt-p38 kinase pathway to reciprocally inhibit GRα but stimulate PPARγ by targeting serine 112 (PPARγ) and serines 220 and 234 (GRα). Here, this mechanism is shown to be essential for GRα and PPARγ control of cellular adipogenesis. In 3T3-L1 cells, FKBP51 was a prominent marker of the differentiated state and knockdown of FKBP51 showed reduced lipid accumulation and expression of adipogenic genes. Compared with wild-type (WT), FKBP51 knockout (51KO) mouse embryonic fibroblasts (MEFs) showed dramatic resistance to differentiation, with almost no lipid accumulation and greatly reduced adipogenic gene expression. These features were rescued by reexpression of FKBP51 in 51KO cells. 51KO MEFs exhibited reduced fatty acid synthase activity, increased sensitivity to GRα-induced lipolysis, and reduced PPARγ activity at adipogenic genes (adiponectin, CD36, and perilipin) but elevated GRα transrepression at these same genes. A p38 kinase inhibitor increased lipid content in WT cells and also restored lipid levels in 51KO cells, showing that elevated p38 kinase activity is a major contributor to adipogenic resistance in the 51KO cells. In 51KO cells, the S112A mutant of PPARγ and the triple S212A/S220A/S234A mutant of GRα both increased lipid accumulation, identifying these residues as targets of the FKBP51/p38 axis. Our combined investigations have uncovered FKBP51 as a key regulator of adipogenesis via the Akt-p38 pathway and as a potential target in the treatment of obesity and related disorders.


Mutation of the Dictyostelium fbxA gene affects cell-fate decisions and spatial patterning.
Cell-fate decisions and spatial patterning in Dictyostelium are regulated by a number of genes. Our studies have implicated a gene called fbxA, which codes for an F-box protein, in these pathways. The FbxA protein is one of the controls on a cAMP phosphodiesterase called RegA, mediating its degradation via ubiquitin-linked proteolysis. Using marked strains, we showed that the fbxA- mutant has defective cell-type proportioning, with a dearth of prestalk cells compared to prespore cells. In this work, we show that this effect occurs earlier during the 24 hour developmental cycle than previously thought. The normal sorting of the prestalk and prespore cells in aggregates and mounds is not affected by the mutation. The mutant cells sort abnormally at the tipped mound stage, when prespore and prestalk cells normally distribute into their proper compartments. The fbxA- mutant forms pre-stalk cells in low numbers when not in chimeras, but in the presence of wild-type amoebae the mutant preferentially forms viable spores, driving the wild type to form non-viable stalk cells. In an attempt to identify the signal transduction pathway that mediates proportionality in prestalk and prespore cells, we asked whether certain signal transduction mutants were immune to the effects of the fbxA- cells and formed spores in chimeras.


Granulomatosis with Polyangiitis (Wegener's Granulomatosis): Evolving Concepts in Treatment.
Granulomatosis with polyangiitis (GPA), formerly termed Wegener's granulomatosis, is the most common of the pulmonary vasculitides. GPA typically involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis. Cardinal histologic features include a necrotizing vasculitis involving small vessels, extensive "geographic" necrosis, and granulomatous inflammation. The spectrum and severity of the disease is heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis. Circulating antibodies against cytoplasmic components of neutrophils (ANCAs) play a role in the pathogenesis, and often correlate with activity of the disease. Treatment strategies are evolving. Cyclophosphamide (CYC) plus corticosteroids was the mainstay of therapy for generalized, multisystemic GPA since the 1970s. However, within the past decade, rituximab (RTX), a monoclonal antibody directed against B cells, has been shown to be at least as effective (and possibly more effective) as CYC. Furthermore, the use of RTX may reduce the need for maintenance immunosuppression. Optimal therapy for GPA remains controversial, and additional studies are required to determine the role and duration of maintenance therapy following successful induction therapy.


Activation of phosphatidylinositol 3-kinase/AKT/snail signaling pathway contributes to epithelial-mesenchymal transition-induced multi-drug resistance to sorafenib in hepatocellular carcinoma cells.
Sorafenib, an orally available kinase inhibitor, is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), and it exerts potent inhibitory activity against epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR) by inhibiting mitogen-activated protein kinase (MAPK) signaling in HCC. However, after long-term exposure to sorafenib, HCC cells exhibit EMT and resistance to sorafenib. The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics. The present study aims to examine the underlying mechanism and seek potential strategies to reverse this resistance and the progression to EMT. Sorafenib-resistant cells showed increased metastatic and invasive ability, with a higher expression of P-glycoprotein (P-gp), compared with the parental cells. This phenomenon was at least partially due to EMT and the appearance of MDR in sorafenib-resistant HCC cells. Moreover, MDR was a downstream molecular event of EMT. Silencing Snail with siRNA blocked EMT and partially reversed the MDR, thereby markedly abolishing invasion and metastasis in sorafenib-resistant HCC cells, but silencing of MDR1 had no effect on the EMT phenotype. Additionally, HCC parental cells that were stably transfected with pCDNA3.1-Snail exhibited EMT and MDR. Two sorafenib-resistant HCC cell lines, established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition but were sensitive to MK-2206, a novel allosteric AKT inhibitor. Thus, the combination of sorafenib and MK-2206 led to significant reversion of the EMT phenotype and P-gp-mediated MDR by downregulating phosphorylated AKT. These findings underscore the significance of EMT, MDR and enhanced PI3K/AKT signaling in sorafenib-resistant HCC cells.


Fusidic acid disk diffusion testing of clostridium difficile can be calibrated using single-strain regression analysis.
Single-strain regression analysis (SRA) was employed to calibrate the disk diffusion antibiotic susceptibility test for fusidic acid and Clostridium difficile. MIC determinations of 40 clinical isolates of C. difficile were performed with the E-test. The disk diffusion test was standardized according to the Swedish Reference Group for Antibiotics (SRGA). Disks used for SRA contained 1.5, 5, 15, 50 and 150 microg fusidic acid and the routine disk contained 50 microg fusidic acid. A control strain, ATCC 9689, was also tested. SRA constants A and B of the regression lines were calculated. This permitted the determination of zone breakpoints for C. difficile. When applying the pharmacological MIC S and R limits set by SRGA to the E-test results I strain of C. difficile was interpreted as resistant. Zone breakpoints corresponding to the pharmacological MIC limits and calculated using the mean SRA constants for the 40 clinical isolates lead to all strains being interpreted as susceptible. SRA calculations enable laboratories to set up calibrated disk tests with species-related and laboratory-specific interpretations.


Microbial Photoelectrosynthesis for Self-Sustaining Hydrogen Generation.
Current artificial photosynthesis (APS) systems are promising for the storage of solar energy via transportable and storable fuels, but the anodic half-reaction of water oxidation is an energy intensive process which in many cases poorly couples with the cathodic half-reaction. Here we demonstrate a self-sustaining microbial photoelectrosynthesis (MPES) system that pairs microbial electrochemical oxidation with photoelectrochemical water reduction for energy efficient H2 generation. MPES reduces the overall energy requirements thereby greatly expanding the range of semiconductors that can be utilized in APS. Due to the recovery of chemical energy from waste organics by the mild microbial process and utilization of cost-effective and stable catalyst/electrode materials, our MPES system produced a stable current of 0.4 mA/cm2 for 24 h without any external bias and ∼10 mA/cm2 with a modest bias under one sun illumination. This system also showed other merits, such as creating benefits of wastewater treatment and facile preparation and scalability.


Etiology of ventricular septal defects: an epidemiologic approach.
To investigate the recent 150% increase in the reported incidence of ventricular septal defects (VSDs) in the United States, the epidemiology of ventricular septal defects was examined. The apparent incidence of VSDs is highly dependent on case finding methods, and more complete diagnosis and reporting probably account for the increase in reported incidence. Variations in case ascertainment also account for the small differences in incidence in studies from different places. The several known risk factors for VSD, including a family history of congenital heart disease and exposure to certain drugs, infectious agents, and maternal metabolic disturbances, explain few cases. Incidence rates are similar in different races and seasons and are unrelated to maternal age, birth order, sex, and socioeconomic status. VSDs occur naturally in a wide range of mammals and in birds, which also have four-chambered hearts. Despite identical genes and similar prenatal environments, the concordance rate in identical twins is only about 10%. The consistency of incidence among individuals with widely differing genes and environments and the frequency of discordance in identical twins suggest that VSDs often occur as random errors in development, at a frequency largely determined by the complexity of normal cardiac morphogenesis. This hypothesis has two major implications: many VSDs are not preventable and parents need not feel responsible for VSDs in their children.


Prevalence of urolithiasis in China: a systematic review and meta-analysis.
To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China. We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random-effects meta-analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates. A total of 46 studies conducted in 22 provinces across China were included in this meta-analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6-11.1%), 7.8% (95% CI 5.8-10.0%), 3.2% (95% CI 0.6-5.7%), 0.5% (95% CI 0.1-0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46-1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis. The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.